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Caption : figure s1. summary of the structures used in this work. (a) structure of trodusquemine labelled with bodipy™ tmr-x and with alexa fluor® 594 on its terminal amine group. (b) mass spectrum of trodusquemine after a treatment of 1 h at 60 °c, i.e. the same time and temperature used to prepare luvs with trodusquemine. the measured mw is 685. (c) mass spectrum of trodusquemine labelled with bodipy™ tmr-x (probe:tro 1:10), showing the peak corresponding to unlabelled trodusquemine (685) and labelled-trodusquemine (1178).

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Caption : figure s2. characterisation of the size and mass of the luvs used in this work. (a) representative dls distribution of luvs composed of dopc/sm 2:1 (mol/mol) + 1% (mol) chol + 1% (mol) gm1. the insets report the apparent hydrodynamic diameter (upper inset), and the pdi (lower inset) as means.e.m. (n=15). (b) representative confocal microscopy image of luvs formed by dopc/sm 2:1 (mol/mol) + 1% (mol) chol + 1% (mol) bodipy-fl-gm1. (c) afm image of slbs obtained from luvs with the same composition as a. the colour bar corresponds to a z range of 20 nm. the scan size is 15 µm. (d) parameters of luvs determined with md simulations and experimental data. all experimental errors are s.e.m.

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Caption : figure s3. structure of the fluorescent labelled lipids used in this work. (a) structure of bodipy-fl-gm1 (gm1-d), whose commercial name is bodipy-fl c5-ganglioside gm1. (b) structure of bodipy-fl-chol (chol-d), whose commercial name is topfluor® cholesterol. (c) structure of cholesteryl 4,4-difluoro-5-(4-methoxyphenyl)-4-bora-3a,4a-diaza-s-indacene-3-undecanoate (chol-a), whose commercial name is cholesteryl bodipy™ 542/563 c11. (d) structure of bodipy-fl-sphingomyelin (sm-d), whose commercial name is topfluor® sphingomyelin. (e) structure of bodipy-fl-dopc (dopc-d), whose commercial name is topfluor® pc.

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Caption : figure s4. trodusquemine exerts its effects in the two-dimensions of the lipid bilayer. (a,b) correlation between the spatial distance (r) between lipids and [tro], [tro]1/2 and [tro]1/3 for gm1-d/chol-a (a) and chol-d/chol-a (b). the data points in all plots were fitted with both a linear and a second-degree polynomial function. all experimental errors are s.e.m. (n=5).